DESCRIPTION (Investigator's abstract): Epidemiological evidence from families with autistic members indicates that there is a strong genetic component to autism. Additionally, there is a sex bias in the prevalence of autism; it is four to eight times more frequent in boys than girls. The objective of the work proposed herein is to identify genes that may be responsible for male specific vulnerability to autism. Recently, researchers in the fields of psychiatry and molecular genetics have focused on the action of a special class of genes known as "imprinted" genes. Most higher organisms have two copies of every gene, one inherited maternally, the other paternally. In most instances, both copies are expressed in the cells of the body. For imprinted genes, however, only one copy is expressed. The decision of which copy of an imprinted gene pair is to be expressed depends upon the parent from which it was inherited. In other words, some genes are only expressed from the paternal chromosome, while others are only expressed from the maternal chromosome. Over thirty genes have been identified in humans and mice that show imprinted patterns of expression. Several of these imprinted genes are known to be involved in developmental disorders in humans. Many of these disorders exhibit neurological symptoms. Furthermore, it has been shown that knockouts of two imprinted genes in mice have profound influences on behavior. It has been hypothesized that an imprinted gene or genes located on the X chromosome may underlie specific social communicative impairment in individuals with Turner's syndrome and that these same genetic loci may be involved in the male susceptibility to autism. Imprinted genes are generally not identified by traditional positional cloning procedures since their distinguishing characteristic is evidenced at the transcriptional level. The specific aim of the proposed work is to identify imprinted genes that are important in neurobehavioral development from mouse models for Turner's syndrome, utilizing screening methods designed to identify genes based on differential transcriptional activity.